Dozens of gut bacteria associated with Multiple Sclerosis gut conditions can change with widely used MS treatment

An international research consortium led by scientists from the University of California, SanFrancisco has demonstrated that there are significant differences between the gut bacterial profiles of patients with multiple sclerosis (MS) and healthy individuals, as well as between MS patients receiving different drug treatments.

This international consortium is composed of researchers from different countries, including the multiple sclerosis research group of the Biodonostia Health Research Institute, led by Dr. Tamara Castillo-Triviño and Dr. David Otaegui with his line of research on microbiota led by Dr. Laura Moles. While some of these changes have been reported previously, most of them are presented for the first time. The group has also discovered new mechanisms by which these bacteria could influence disease development and response to treatment.

In recent years, scientists have increasingly established connections between gut bacteria and a range of diseases – not just those of the gut – such as diabetes and arthritis and other diseases centered on the nervous system. The field of microbiome studies really opened up with advances in DNA sequencing in the early 2010s, which allowed scientists to get a detailed picture of the bacteria present in stool, blood, mucosal tissue and skin samples.

Until recently, most of the experimental evidence suggesting a link between gut bacteria and MS came from research in mice. Studies in humans had provided inconsistent results, in part because of smaller numbers of participants and because the effects of the environment on the individual’s microbiome had not been analyzed. Where you live-rural or urban, on top of a mountain or next to an oil refinery-plays an important role in what bacteria your body harbors.

To get around these limitations, the consortium of scientists involved in the International Multiple Sclerosis Microbiome Study (IMSMS) recruited a large number of MS patients from three continents and selected genetically unrelated controls from the same households as the patients. This is the first time this methodology has been used in such a large study. The study, published in Cell on September 15, 2022, describes differences between the gut microbiome profiles of 576 patients and an equal number of household controls from the United States, Canada, United Kingdom, Germany, Spain, and Argentina. The findings could lead to new therapies involving manipulation of the microbiome or dietary interventions.

With an innovative protocol, dozens of new species of bacteria associated with MS have been identified and other species that had previously only been associated with the disease have been confirmed. “We were surprised by the number of species that were differentially present in MS compared to controls,” Baranzini said. They also found that the largest source of variation in bacterial species was related to the geographic location of the participants, confirming the importance of location and local variations in diet for the gut microbiome. The second most important source of variation was the participant’s disease status, which is what the researchers expected.

The iMSMS group will continue to recruit patients until the total number of participants in the cohort reaches 2000. Starting this fall, they will also follow a subset of patients for two years to see how their gut microbiota changes in response to treatment, lifestyle changes and disease progression. All data from these studies will be made public. This work is an example of where science is headed; collaborative, international studies with strong consortia are needed to jointly address such ambitious goals as understanding the role of the microbiota in disease.